Background: Myeloid sarcoma (MS) is a rare extramedullary tumor composed of immature myeloid cells that can precede, coincide with, or follow acute myeloid leukemia (AML). Although its clinicopathologic features have been described in case series, its molecular genetic aberrations have rarely been reported. We assessed the molecular genetic features of de novo MS.Design: We searched the database of our hospital (01/2002-09/2012) for cases of de novo MS with or without bone marrow (BM) involvement at initial diagnosis. Clinical data were obtained from medical records. Mutational analyses were performed for FLT3 and NPM1 (PCR/capillary electrophoresis), NRAS/KRAS and JAK2 (pyrosequencing), KIT and CEBPA (Sanger sequencing) and IDH1/IDH2 (high-resolution melting curve analysis). Statistic analyses were performed using student t-test, Fisher exact test and Kaplan-Meier method.Results: We identified 63 cases of de novo MS (34 men and 29 women, median age 50 years, range 1-80). At initial presentation, 32 patients had no BM involvement (non-leukemic group, 17 men and 15 women, median age 48 years, range 1-80), and 31 had BM involvement (leukemic group, 17 men and 14 women, median age 31 years, range 8-76). Skin was the most frequently involved site in non-leukemic and lymph nodes were the most commonly affected site in leukemic group. Patients with leukemic MS had higher WBC (7.6k/µL vs 7.0k/µL, p<0.04), lower hemoglobin (10.6g/dL vs 13.7g/dL, p<0.005), lower platelet (132k/µL vs 268k/µL, p<0.0001) and higher LDH (1002IU/L vs 454IU/L, p<0.01). With a median follow-up of 6 months, 8 patients with non-leukemic MS developed BM disease 1.5-42 months after initial presentation. Cytogenetic abnormalities were detected in 5/7 non-leukemic and 19/30 leukemic cases. Trisomy 8 occurred more frequently in leukemic cases. FLT3-ITD was detected in 4/23 leukemic and 0/6 non-leukemic cases. Mutations of other genes included NPM1 (2/9), CEBPA (1/4), and NRAS (1/20) in leukemic and NPM1 (1/1) in non-leukemic group. No mutation was identified in KRAS, KIT, JAK2, IDH1 or IDH2. All patients received multi-agent chemotherapy; 11 received BM transplantation (6 leukemic, 5 non-leukemic). With a median follow-up of 17 months (range 1-135), patients with non-leukemic MS had significantly longer event-free survival (p<0.05) and overall survival (p<0.05) than leukemic MS.Conclusions: Patients with non-leukemic MS have significantly better event-free and overall survival than leukemic MS. Trisomy 8 and FLT3-ITD are more common in leukemic MS, which may contribute to its worse prognosis.Category: Hematopathology